The U.S. Food and Drug Administration (FDA) has granted Fast Track Designation to DB-1303 a novel antibody-drug conjugates (ADC) for the treatment of patients with advanced, recurrent or metastatic endometrial carcinoma with HER2 over-expression who have progressed on or after standard systemic treatment.

Endometrial carcinoma is the most common cancer of the female genital tract.  In early 2019 an estimated 822,388 people were living with uterine corpus cancer in the United States. and according to available data, an  estimated that 66,200 new uterine corpus cancer cases will occur with 13,030 deaths resulting from the disease in 2022.

Around 1 in 4 women with endometrial cancer may experience a recurrence or be diagnosed with advanced disease. In endometrial cancer, approximately 60%–70% of high-grade carcinomas appear to over-express HER2.

Patients diagnosed with advanced endometrial carcinoma have limited treatment options. And while there some treatment options are demonstrating promising anti-tumor activity in patients with advanced endometrial carcinoma who have experienced disease progression after prior treatment with platinum-based systemic therapy with or without immunotherapy, there is currently no accepted standard of care, limited therapeutic options for these patients.

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Fertility concern
Endometrial carcinoma is typically diagnosed in postmenopausal women. In most cases the disease is diagnosed in an early stage (80% in stage I), with 5-year survival rates over 95%. Most endometrial cancer cases are sporadic, with only 10% a considered familiar cancer. [1] And while the diagnosis of this disease in young women of childbearing age is rare (Between 4% and 5% of diagnosed patients are <40 years of age), the standard approach for the management of endometrial cancer in young women of childbearing age is hysterectomy and bilateral salpingo-oophorectomy with or without lymphadenectomy.  This is, however, not an ideal treatment option for women trying to have a baby or are just thinking about it, and a more conservative treatment approach, including uterine and ovarian preservation, may be used for patients women who have a strong desire to maintain fertility in spite of potential oncologic risks. [1][2]

Anti-HER2 therapy has recently emerged as an effective targeted treatment approach for patients diagnosed with advanced air recurrent endometrial carcinoma, resulting in significantly prolonged progression-free and overall survival when combined with chemotherapy.[3]

A novel treatment option
To meet the significant unmet medical need of patients diagnosed with endometrial carcinoma, Duality Biologics, a clinical-stage biotech company focused on discovering and developing a pipeline of antibody-drug conjugates (ADCs) targeting cancers and autoimmune diseases, is developing DB-1303,  an investigational antibody-drug conjugate or ADC comprised of anti-HER2 antibody, enzymatically cleavable peptide-linker, and a proprietary topoisomerase I inhibitor P1003. The drug is designed to have potent anti-tumor activity and bystander killing effect, high plasma stability, low free payload in circulation and wide therapeutic index.

DB-1303 is a 3rd generation HER2 ADC based on Duality Biologics’ Proprietary DITAC (Duality Immune Toxin Antibody Conjugates) technology platform.  The investigational agent exhibited potent anti-tumor activity in both HER2 positive and HER2 low tumor models with superior efficacy, safety and expanded therapeutic window. Both preclinical data and preliminary clinical data from DB1303 suggest the potential of DB-1303 to address unmet medical needs in various HER2 expressing cancers.

John Zhu, PhD, MBA, founder and Chief Executive Officer of DualityBio.

Fast track designation
The FDA’s Fast Track Designation facilitates the development and expedite the review of drugs to treat serious conditions and fulfill an unmet medical need, enabling drugs to reach patients earlier. Clinical programs with Fast Track designation may benefit from early and frequent communication with the FDA throughout the regulatory review process.

These clinical programs may also be eligible to apply for Accelerated Approval and Priority Review if relevant criteria are met.

“The FDA’s decision to grant FTD underscores the potential for DB-1303 to address the unmet medical need and potentially serve as a new therapeutic option for patients with advanced, recurrent or metastatic endometrial carcinoma,” noted John Zhu, PhD, MBA, founder and Chief Executive Officer of Duality Biologics.

“We are committed to advance DB-1303 to help those patients who are suffering from cancers. We will work closely with clinical investigators and health authorities to unlock the full potential of this investigational agent in patients with malignant tumors.”

DualityBio is currently evaluating DB-1303 in an ongoing Phase I/IIa clinical trial for preliminary safety and efficacy in advanced/metastatic solid tumors with Her2 expression, including both HER2 positive and HER2 low patients.

Leveraging its DITAC (Duality Immune Toxin Antibody Conjugates) and DIMAC (Duality Immune Modulating Antibody Conjugates) technology platforms, Duality Biologics is currently developing more than 10 ADCs at clinical and preclinical stage.

Clinical trials
A Study of DB-1303 in Advanced/Metastatic Solid Tumors – NCT05150691

[1] Zivanovic O, Carter J, Kauff ND, Barakat RR. A review of the challenges faced in the conservative treatment of young women with endometrial carcinoma and risk of ovarian cancer. Gynecol Oncol. 2009 Dec;115(3):504-9. doi: 10.1016/j.ygyno.2009.08.011. Epub 2009 Sep 15. PMID: 19758691.
[2] Carneiro MM, Lamaita RM, Ferreira MC, Silva-Filho AL. Fertility-preservation in endometrial cancer: is it safe? Review of the literature. JBRA Assist Reprod. 2016 Dec 1;20(4):232-239. doi: 10.5935/1518-0557.20160045. PMID: 28050959; PMCID: PMC5265623.
[3] Buza N. HER2 Testing and Reporting in Endometrial Serous Carcinoma: Practical Recommendations for HER2 Immunohistochemistry and Fluorescent In Situ Hybridization: Proceedings of the ISGyP Companion Society Session at the 2020 USCAP Annual Meeting. Int J Gynecol Pathol. 2021 Jan;40(1):17-23. doi: 10.1097/PGP.0000000000000711. PMID: 33290351.

Featured Image: Doctor talking to African American patient. Courtesy: © 2017 – 2023. Fotolia/Adobe. Used with permission.

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